Large numbers of individuals in the United States and elsewhere suffer from constant debilitating pain. These individuals include victims of terminal diseases and chronic diseases such as osteoarthritis.
Ongoing attempts have been made to provide a more potent analgesic which can be self-administered and which is nonaddicting. While certain well-known and effective analgesics, such as morphine and heroin, are in fact available, they lack useful oral activity, and because of their potential for abuse, their use has been restricted, and the most effective forms have been denied even to terminal patients because of the vulnerability of supplies to theft.
Research to provide an effective but nonaddicting analgesic has understandably centered around structural analogs of the naturally occurring codeine and morphine compounds. A number of N-sec-alkyl analogs of norcodeine and normorphine have been prepared and are described in U.S. Pat. Nos. 4,269,843 and 4,218,454. A number of these N-.alpha.-methylhydrocarbyl derivatives were reported to have biological activity, and a number of them were capable of resolution into the two diastereomeric forms generated with respect to the chiral center at the .alpha.-carbon. Among those compounds not separable was N-.alpha.-methylcyclopropylmethyl normorphine and the corresponding norcodeine. While the diastereomeric mixtures of these compounds are reasonably active as analgesics in standard assays, it has now been found that separation into the diastereomers results in a uniquely active preparation with expected low addictive potential. In addition, an alternative method to prepare these .alpha.-methylalkylmethyl analogs using the corresponding ketones has been found.